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The analysis of GSTA1 promoter genetic and functional diversity of human populations
- Source :
- Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021), Scientific Reports, Scientific reports, Vol. 11, No 1 (2021) P. 5038
- Publication Year :
- 2020
-
Abstract
- GSTA1 encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTA1 has several functional SNPs within its promoter region that are responsible for a change in its expression by altering promoter function. This study aims to investigate distributions of GSTA1 promoter haplotypes across different human populations and to assess their impact on the expression of GSTA1. PHASE 2.1.1 was used to infer haplotypes and diplotypes of six GSTA1 promoter SNPs on 2501 individuals from 26 populations classified by the 1000 Genomes Project into five super-populations that included Africa (N = 660), America (N = 347), East Asia (N = 504), Europe (N = 502), and South Asia (N = 488). We used pairwise FST analysis to compare sub-populations and luciferase reporter assay (LRA) to evaluate the impact of each SNP on activation of transcription and interaction with other SNPs. The distributions of GSTA1 promoter haplotypes and diplotypes were significantly different among the different human populations. Three new promoter haplotypes were found in the African super-population. LRA demonstrated that SNPs at -52 and -69 has the most impact on GSTA1 expression, however other SNPs have a significant impact on transcriptional activity. Based on LRA, a new model of cis-elements interaction is presented. Due to the significant differences in GSTA1 diplotype population frequencies, future pharmacogenomics or disease-related studies would benefit from the inclusion of the complete GSTA1 promoter haplotype based on the newly proposed metabolic grouping derived from the LRA results.
- Subjects :
- Asia
Transcription, Genetic
Population genetics
Science
Population
Single-nucleotide polymorphism
Biology
030226 pharmacology & pharmacy
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
0302 clinical medicine
Transcription (biology)
Genes, Reporter
SNP
Humans
ddc:576.5
1000 Genomes Project
education
Luciferases
Promoter Regions, Genetic
Glutathione Transferase
Genetics
education.field_of_study
ddc:618
Multidisciplinary
Binding Sites
Molecular medicine
Genome, Human
Medical genetics
Haplotype
Promoter
Hep G2 Cells
Europe
Genetics, Population
Gene Expression Regulation
Haplotypes
030220 oncology & carcinogenesis
Pharmacogenomics
Africa
Genetic markers
Medicine
Gene expression
Americas
Biomarkers
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....b72bfe8ad171c502fb082ac518ecca05